The use of synthetic materials in the field of cardiovascular surgery and particularly in the reconstruction of the vascular system has been one of the greatest advances in this field. The materials used must not only possess suitable physicochemical properties such as flexibility, hydrolytic stability and fatigue strength, but it is essential that they exhibit a good blood biocompatibility or hemocompatibility. The contact of the prosthetic devices with the blood flow leads to the deposition of plasmatic proteins on the surface of the material and to the activation of the coagulation cascade, generating a thrombogenic surface.
No material has yet been found that can be regarded in a strict sense as non-thrombogenic, although certain materials have been used with success in the manufacture of big-diameter (>6 mm) vascular prostheses. Thus, for example, during the last decades commercially available synthetic vascular grafts based mainly on meshes woven or knitted with polyester (Dacron®), polyamide (Nylon®) or polytetrafluoroethylene (PTFE, Teflon®) fibres as well as porous, expanded PTFE (Goretex®) systems have been used. Whereas this type of prostheses works relatively well when used to substitute big-diameter vessels, the failure rate at short- or mid-term is quite high when they are used to substitute small- or medium-calibre vessels due to the appearance of thrombosis. It is therefore still necessary to improve the materials used up to now for this kind of applications.
Triflusal, whose chemical name is 2-acetyloxy-4-trifluoromethylbenzoic acid, is a platelet aggregation inhibitor marketed for the treatment of thromboembolic disorders. Its main metabolite, known by the acronym HTB and whose chemical name is 2-hydroxy-4-trifluoromethylbenzoic acid, also exhibits a remarkable platelet aggregation-inhibitory activity. Both compounds are disclosed in the patent U.S. Pat. No. 4,096,252.
The present invention provides a new series of biocompatible polymeric derivatives carrying triflusal or HTB, which, when used as coatings for the surface of prostheses and other devices that are in contact with blood during use, improve the thrombogenic properties of said devices.